Elucidation of the genetics involved in cognitive dysfunction is important for potential therapeutic and educational intervention. Over the past decade, much attention has focused on the role of genetics in specific types of cognitive dysfunction in children and the elderly. In some cases specific genes have been implicated (e.g., Alzheimer's disease). However, cognition is complex and there are many genes that influence it. Our long-term goal is to find genes involved in learning inefficiencies, so that treatments can be devised to help those with cognitive impairments. The objective of this application is to examine the role of genetics in spatial learning. Spatial learning provides us with a representation of objects in the world around us and is critical for everyday cognition. Three measures of spatial learning in rodents, the Barnes Maze (BM), the Morris water maze (MWM) and the Spatial/ Object Novelty in the Open Field Assay (SON) will be used in this research project. We propose to investigate the role of genetics in all three assays, by evaluating multiple measures of performance. The specific aims of this application are: 1). Evaluate potential order effect when testing the same mice in i) both the BM and MWM and ii) both spatial and cued versions of the MWM, 2). Determine genetic loci involved in spatial learning and memory as measured by our behavioral test battery, and 3). Confirm and/or narrow down genetic loci with knockout/ congenic strains. We will eventually use genomic techniques to identify candidate genes, however, this is beyond the scope of the present grant proposal. As this is our first venture into the genetic dissection of spatial learning and memory, this project is exploratory in nature and therefore is being submitted as an Exploratory/Developmental Research (R21) grant. Our preliminary data provides evidence that multiple measures will yield a plethora of information on inbred strain performance differences in spatial learning and memory. More detailed analyses of the paths used by the mice to navigate the BM MWM should provide even more in-depth information. This new, exciting line of investigation should have high impact on the field, by providing baseline data of spatial learning and memory performance for commonly used in strains as well as providing genetic loci for future investagion.